The major aim of this proposal is to characterize the biological and molecular profile of DR antigens, a set of histocompatibility antigens expressed on human B lymphoid cells. The immunogenic properties of DR antigens in allogeneic and xenogeneic combinations will be investigated. The expression of DR antigens in body fluids from leukemic patients will be measured and correlated with the clinical course of disease. (We will investigate immunological crossreactivity between human DR and murine Ia antigens by serological and immunochemical means, since we found considerable homology between both alpha- and beta-chains of these molecules when we recently determined the partial N-terminal amino acid sequence of DR antigens. If such crossreactivity is found, this property will be combined with other approaches for developing a number of specific xenoantisera to human DR antigens, since our previous work showed that xenoantisera to human histocompatibility antigens can recognize allotypic specificities). The specificity of these xenoantisera will be compared to that of alloantisera by utilizing serological and immunochemical tests. (Once characterized, specific xenoantisera will be used as molecular probes to investigate the molecular structure and amino acid sequence of human DR antigens with various allotypic specificities). (The fesibility of this approach has already been established. For example, we recently demonstrated that the initial DR xenoantisera developed by us are suitable for sufficiently purifying DR antigens by indirect immunoprecipitation to determine the partial amino acid sequence of their alpha- and beta-chains.) Efforts will also be made to determine the molecular structure of the smallest fragment with antigenic activity and thus to elucidate the chemical composition of allotypic sites. The information acquired from these studies should facilitate a better understanding of the molecular basis of DR antigens' polymorphism, elucidate the role of DR antigens in susceptibility to disease and thus suggest novel approaches for the treatment of diseases resistant to conventional therapy.